Faecal concentrations of short-chain fatty acids and selected bacteria in healthy and celiac children

Background: Knowledge about the interplay between diet, microbiota and short-chain fatty acids (SCFAs) so far exists. Moreover, raising evidence suggests their influence on the pathogenesis of the celiac disease (CD). Objective: Our aim was to study and evaluate differences in the composition of selected bacterial groups and SCFAs in faeces of healthy and CD children. Methods: The study included 41 children with CD, 8 newly discovered, not treated children (ND) and 33 children on gluten-free diet for more than 1 year (GFD) and 17 healthy children as a Control group. Bacterial communities and SCFAs in faecal samples were determined by real-time PCR and HPLC analysis, respectively. Results: There were no statistically significant differences between GFD and ND patients. GFD patients compared to Controls had significantly lower Lactobacillus spp. (p = 0.027) and Enterobacteriaceae family group (p = 0.003), but higher propionic acid (p = 0.034). Acetic (p = 0.027) and propionic acid (p = 0.014) were significantly higher in ND patients compared to Controls. Lactobacillus spp. negatively correlated with total SCFAs in the Control and the ND group. In ND and GFD patients, Lactobacillus spp. negatively correlated with Clostridium sensu stricto cluster I. A very strong positive correlation (p = 0.002) between Enterobacteriaceae family and Bacteroides fragilis was found in GFD patients. Conclusions: Changes in microbiota and SCFAs are clearly related to the pathogenesis of CD. As being potential pro-inflammatory agents in CD, acetic and propionic acid may serve as important disease-related markers. Their origin in relation to Lactobacillus and Bifidobacterium is debatable and still need to be further investigated. Enterobacteriaceae family might not be directly addressed to pathogenesis of CD

The residual service life of the riveted railway bridge

Opisano je določevanje preostale uporabnosti kovičenega jeklenega železniškega mostu čez Dravo na Ptuju. Izračun temelji na metodah mehanike loma, na integraciji Parisove funkcije. Za začetno velikost napake vzamemo hipotetično razpoko, ki je skrita pod glavo kovice, kritično velikost razpoke pa določimo z merjenjem kritične vrednosti J-integrala ter z uporabo znane Sedlackekove odvisnosti J proti a, pri čemer je a velikost razpoke.The residual service life of the riveted railway bridge across the Drava river near Ptuj is described. The calculation is based on fracture mechanics concepts, on the integration of Paris function. The hypothetical crack hidden under the heat of the rivet was considered as initial flaw, whereas the critical crack size was determined by measuring the critical value of J-integral and J vs. a relationship proposed by Sedlacek, where a is the crack size. Specimens were made from a steel lamella from a diagonal brace and the crack propagation rate and the fracture toughness of the steel were measured. All the measurements were performed at room temperature and at -20°C. the Paris function with threshold stress intensity range ▫$K_{th}$▫ was measured whereas the ▫$J_{lc}$▫ integral was estimated on the basis of the known ▫$K_{lc}$▫ values. Some of the ▫$J_{lc}$▫ were measured directly too. The results are given as a number of cycles which can provoke a critical cracklengthening and are a reliable base for determining the frequency of detectoscopic inspections of vital elements of the bridge

Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

Objective: To ascertain possible determinants of carbamazepine (CBZ)\u2013 and oxcarbazepine (OXC)\u2013induced hyponatremia in a large cohort of people with epilepsy. Methods: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ 64134 mEq/L and severe hyponatremia as Na+ 64128 mEq/L. Results: We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively. Significance: Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on

Assessing the role of rare genetic variants in drug-resistant, non-lesional focal epilepsy

Objective: Resistance to antiseizure medications (ASMs) is one of the major concerns in the treatment of epilepsy. Despite the increasing number of ASMs available, the proportion of individuals with drug-resistant epilepsy remains unchanged. In this study, we aimed to investigate the role of rare genetic variants in ASM resistance. Methods: We performed exome sequencing of 1,128 individuals with non-familial non-acquired focal epilepsy (NAFE) (762 non-responders, 366 responders) and were provided with 1,734 healthy controls. We undertook replication in a cohort of 350 individuals with NAFE (165 non-responders, 185 responders). We performed gene-based and gene-set-based kernel association tests to investigate potential enrichment of rare variants in relation to drug response status and to risk for NAFE. Results: We found no gene or gene set that reached genome-wide significance. Yet, we identified several prospective candidate genes – among them DEPDC5, which showed a potential association with resistance to ASMs. We found some evidence for an enrichment of truncating variants in dominant familial NAFE genes in our cohort of non-familial NAFE and in association with drug-resistant NAFE. Interpretation: Our study identifies potential candidate genes for ASM resistance. Our results corroborate the role of rare variants for non-familial NAFE and imply their involvement in drug-resistant epilepsy. Future large-scale genetic research studies are needed to substantiate these findings